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Detection of triethylenemelamine-induced translocation heterozygotes in CD-1 mice: fertility and cytological methods
Abstract:
A study was conducted to determine the extent to which translocation carriers can be missed in the heritable translocation test. CD-1 male mice were treated with the mutagen triethylenemelamine and bred to untreated females and male progeny were subjected to fertility and cytogenetic analyses. Fertility testing involved mating 1 male to 3 virgin females and subjecting the females to uterine analysis. The males were classified as having normal or reduced fertility according to the number of live implants produced by the females. The cytogenetic analysis involved scoring 25 primary spermatocytes per mouse for translocation multivalents. A total of 103 male progeny were analyzed. Evaluation of fertility and cytogenetic data confirmed the presence of 18 translocation heterozygotes among the male progeny. On the basis of fertility testing, 1 translocation heterozygote was classified as normal (false negative) based on the production of 11 or more live implants by at least 1 mated female. On the basis of cytogenetic analysis of 25 cells per mouse, 1 partially sterile male was classified as normal (false negative); however, analysis of additional cells showed that this mouse was a translocation heterozygote. The study demonstrates the importance of evaluating fertility and cytogenetic criteria to minimize the extent of misclassification in conducting a heritable translocation test.
Insights
This study investigated the heritable translocation test in mice, finding that combining fertility and cytogenetic analyses is crucial. Evaluating both methods minimizes misclassifying translocation carriers, ensuring accurate genetic testing results.
Area of Science:
- Genetics
- Toxicology
- Reproductive Biology
Background:
- The heritable translocation test is vital for assessing mutagenicity.
- Accurate identification of translocation carriers is essential for risk assessment.
Purpose of the Study:
- To determine the rate at which translocation carriers are missed in the heritable translocation test.
- To evaluate the effectiveness of combined fertility and cytogenetic analyses in identifying carriers.
Main Methods:
- CD-1 male mice were exposed to the mutagen triethylenemelamine.
- Male progeny underwent fertility testing (mating males to females, uterine analysis) and cytogenetic analysis (scoring spermatocytes for translocations).
Main Results:
- Eighteen translocation heterozygotes were identified among 103 male progeny.
- One translocation heterozygote was initially misclassified as normal (false negative) by fertility testing alone.
- Another translocation heterozygote was initially missed by cytogenetic analysis of 25 cells but identified upon further examination.
Conclusions:
- Sole reliance on fertility testing or limited cytogenetic analysis can lead to false negatives in the heritable translocation test.
- Integrating comprehensive fertility and detailed cytogenetic evaluations is critical to minimize misclassification of translocation carriers.
- This integrated approach enhances the accuracy and reliability of the heritable translocation test for genetic risk assessment.